Methods and compositions for treating huntington's disease

Abstract

Disclosed herein are compositions comprising non-naturally occurring zinc finger domains, fusion proteins comprising these zinc finger domains, polynucleotides encoding these proteins, cells expressing these proteins and pharmaceutical compositions comprising these proteins or polynucleotides as well as methods of modifying an Htt gene using these compositions for treating or preventing Huntington's Disease.

1 .- 9 . (canceled) 
     
     
         10 . A non-naturally occurring TALE transcription factor (TALE-TF) that binds to an Htt gene, the TALE-TF comprising a fusion protein comprising a TALE DNA binding domain linked to a transcriptional repression domain, wherein the TALE DNA binding domain comprises an amino acid sequence of any one of SEQ ID NOs: 197, 198, or 199, wherein the transcriptional repression domain comprises an amino acid sequence of any one of SEQ ID NOs: 210, 211, or 212, and wherein the TALE-TF specifically binds to a mutant Huntington's gene allele (mHtt) comprising a nucleic acid sequence of any one of SEQ ID NOs: 200-207. 
     
     
         11 . An mRNA encoding the non-naturally occurring TALE-TF of  claim 10 . 
     
     
         12 . A host cell comprising the non-naturally occurring TALE-TF of  claim 10 . 
     
     
         13 . A pharmaceutical composition comprising an mRNA according to  claim 11 . 
     
     
         14 . A method of modifying expression of an mHtt gene in a cell, the method comprising administering to the cell one or more polynucleotides encoding the non-naturally occurring TALE-TF of  claim 10 . 
     
     
         15 . A method of treating Huntington's Disease, the method comprising administering an mRNA according to  claim 10  to a subject in need thereof. 
     
     
         16 . A method of treating Huntington's Disease comprising administering the pharmaceutical composition according to  claim 13  to a subject in need thereof. 
     
     
         17 . The method of  claim 15 , wherein the mRNA is administered to the striatum of the subject. 
     
     
         18 . The method of  claim 16 , wherein the pharmaceutical composition is administered to the striatum of the subject.